Colorectal cancer vaccines: Tumor-associated antigensvsneoantigens

Abstract

Therapeutic options for the treatment of colorectal cancer (CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hyper-mutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens (TAAs) and tumor-specific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptide-based vaccines achievable by adjuvants and immune-stimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens - in CRC almost exclusively neoantigens - which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immune-stimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine’s requirements and will manifest as treatment pillar for routine clinical management of CRC.

Ongoing and future directions in the management of metastatic colorectal cancer: Update on clinical trials

“…The goal of these vaccines is to prevent cancer from developing (preventative vaccines) or incite the immune system of patients with the active disease to stop further growth or as an adjuvant to standard chemotherapy to destroy remaining cancer cells left after standard therapy . Different sources of developing these vaccines include TAAs, cancer peptides, peptide‐expressing viruses, peptide‐loaded antigen presenting cells, or application of peptide‐specific T cells . Based on their mode of action or source of development, cancer vaccines are classified as antigen vaccines, DNA vaccines, whole cell vaccines, dendritic cell vaccines, or DC vaccines, and anti‐idiotype vaccine .…”

“…Source of these vaccines include adenovirus, listeria monocytogenes, bifidobacterium, modified recombinant viral vectors, RNA reovirus, herpes simplex virus, and tetanus toxoid peptides. Main targets of cancer vaccines include TAAs including CEA (carcinoma embryonic antigen), MAGE (melanoma‐associated antigen), MUC1, Survivin, WT1, ring finger protein 43 (RNF43), TOMM34, FOXM1, VEGFR‐1/2, KOC1, and others …”

“…Identification of tumor antigens remains a challenge, and hence tumors with high mutation burden or phenotypes (eg, MSI‐H) that produce high amounts of neoantigens or peptides show promising results . Several different forms of vaccines are being currently investigated for the treatment of mCRC.…”

“…28 Different sources of developing these vaccines include TAAs, cancer peptides, peptide-expressing viruses, peptide-loaded antigen presenting cells, or application of peptide-specific T cells. 29 Based on their mode of action or source of development, cancer vaccines are classified as antigen vaccines, DNA vaccines, whole cell vaccines, dendritic cell vaccines, or DC vaccines, and antiidiotype vaccine. 28 The first cancer vaccine to be FDA approved was sipuleucel-t (Provenge) which is an autologous vaccine directed against prostate cancer and has shown to improve OS for men with treatment-resistant or metastatic prostate cancer (mPC).…”

Adoptive Cell Therapy—Harnessing Antigen-Specific T Cells to Target Solid Tumours

“…The perfect targets for T cell-based therapies are tumour-specific antigens called also neoantigens, as they are highly immunogenic and not produced by normal tissues [63]. They can be either products of non-synonymous mutations in cancer genome or viral-specific proteins expressed by virally-induced tumours such as cervical and head and neck cancer associated with human papilloma virus (HPV) and Epstein-Barr virus (EBV) infection, respectively [64,65].…”